Faculty Opinions recommendation of Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients.

While improvements in pre-hospital and in-hospital care allow more multiple trauma patients to advance to intensive care, the incidence of posttraumatic multiple organ dysfunction syndrome (MODS) is on the rise. Herein, the influence of a selective IL-6 trans-signaling inhibition on posttraumatic cytokine levels was investigated as an approach to prevent MODS caused by a dysbalanced posttraumatic immune reaction. Therefore, the artificial IL-6 trans-signaling inhibitor sgp130Fc was deployed in a murine multiple trauma model (femoral fracture plus bilateral chest trauma). The traumatized mice were treated with sgp130Fc (FP) and compared to untreated mice (WT) and IL-6 receptor knockout mice (RKO), which received the same traumas. The overall trauma mortality was 4.4%. Microscopic pulmonary changes were apparent after multiple trauma and after isolated bilateral chest trauma. Elevated IL-6, MCP-3 and RANTES plasma levels were measured after trauma, indicating a successful induction of a systemic inflammatory reaction. Significantly reduced IL-6 and RANTES plasma levels were visible in RKO compared to WT. Only a little effect was visible in FP compared to WT. Comparable cytokine levels in WT and FP indicate neither a protective nor an adverse effect of sgp130Fc on the cytokine release after femoral fracture and bilateral chest trauma.

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Cell-free nuclear, but not mitochondrial, DNA concentrations correlate with the early host inflammatory response after severe trauma

Scientific Reports ◽

10.1038/s41598-019-50044-z ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Julie A. Stortz ◽

Russell B. Hawkins ◽

David C. Holden ◽

Steven L. Raymond ◽

Zhongkai Wang ◽

...

Keyword(s):

Gene Expression ◽

Mitochondrial Dna ◽

Inflammatory Response ◽

Nuclear Dna ◽

Severe Trauma ◽

Organ Injury ◽

Trauma Patients ◽

Chronic Critical Illness ◽

Molecular Patterns ◽

The Relationship

Abstract Severe blunt trauma is associated with an early ‘genomic storm’ which causes simultaneous up- and down-regulation of host protective immunity. Excessive inflammation can lead to organ injury. In the absence of infection, the inflammatory response is presumably driven by release of endogenous alarmins called danger-associated molecular patterns (DAMPs), which initiate immune responses through pattern-recognition receptors (PRR). Here we examined the relationship between concentrations of cell-free (cf) nuclear DNA (ncDNA) and mitochondrial DNA (mtDNA) within 24 hours post trauma with circulating leukocyte transcriptomics and plasma IL-6 concentrations, as well as the patients’ clinical trajectories. In 104 patients enrolled from two level-1 trauma centers, ncDNA and mtDNA concentrations were increased within 24 hours of severe trauma, but only ncDNA concentrations correlated with leukocyte gene expression and outcomes. Surprisingly, ncDNA, not mtDNA concentrations, were significantly elevated in trauma patients who developed chronic critical illness versus rapid clinical recovery. Plasma IL-6 and leukocyte transcriptomics were better predictors of outcomes than cfDNA levels. Although mtDNA and ncDNA are significantly increased in the immediate post-trauma period, the dramatic inflammatory and gene expression changes seen after severe trauma are only weakly correlated with ncDNA concentrations, and more importantly, mtDNA concentrations are not associated with adverse clinical trajectories.

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Plasma levels of insulin-like growth factor binding protein-3 in acute trauma patients

Metabolism ◽

10.1016/0026-0495(95)90017-9 ◽

1995 ◽

Vol 44 (9) ◽

pp. 1205-1208 ◽

Cited By ~ 16

Author(s):

Malayappa Jeevanandam ◽

Nancy J. Holaday ◽

Scott R. Petersen

Keyword(s):

Growth Factor ◽

Plasma Levels ◽

Binding Protein ◽

Trauma Patients ◽

Insulin Like Growth Factor ◽

Acute Trauma ◽

Factor Binding

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P12.02 Systemic Anticancer Therapy Upregulate Plasma Levels of Damage-Associated Molecular Patterns in Patients With Advanced Lung Cancer

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2021.08.324 ◽

2021 ◽

Vol 16 (10) ◽

pp. S1007

Author(s):

H. Inoue ◽

H. Tsutsumi ◽

K. Tanaka ◽

E. Iwama ◽

Y. Yoneshima ◽

...

Keyword(s):

Lung Cancer ◽

Plasma Levels ◽

Anticancer Therapy ◽

Advanced Lung Cancer ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

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Scavengers of hemoproteins as potential biomarkers for severe sepsis and septic shock

Translational Medicine Communications ◽

10.1186/s41231-021-00088-z ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Myrddin W. Verheij ◽

Ingrid Bulder ◽

Walter A. Wuillemin ◽

Carlijn Voermans ◽

Sacha S. Zeerleder

Keyword(s):

Septic Shock ◽

Severe Sepsis ◽

Plasma Levels ◽

Mitochondrial Damage ◽

Heme Oxygenase 1 ◽

Healthy Donors ◽

Droplet Pcr ◽

Sepsis And Septic Shock ◽

Molecular Patterns ◽

Damage Marker

Abstract Background Despite improvements in diagnosis, interventions and supportive care, mortality among sepsis patients is still high. Research of the past decade has attempted to identify biomarkers that can accurately discriminate sepsis from other diseases with comparable symptoms to improve diagnosis, but results have been lackluster. Recent studies have shown that hemoproteins and damage-associated molecular patterns (DAMPs) such as mitochondrial DNA (mtDNA) released as the result of hemolysis play an important role in the pathogenesis of sepsis. The aim of this study was to measure plasma levels of the indirect markers for hemoproteins hemopexin, haptoglobin and heme oxygenase-1 (HO-1) as well as the mitochondrial damage marker mtDNA in the plasma of a cohort of sepsis patients to determine the feasibility of their use as biomarkers in the diagnosis of sepsis. Methods Hemopexin, haptoglobin and HO-1 were measured in plasma by ELISA and mtDNA was measured by digital droplet PCR. Plasma levels of hemopexin, haptoglobin, HO-1 and mtDNA were measured in 32 patients with severe sepsis and 8 patients with septic shock at baseline and 4 days after admission to the ICU and in 20 healthy donors. Results Plasma levels of hemopexin were significantly lower and plasma levels of HO-1, haptoglobin and mtDNA were significantly higher in patients with severe sepsis and septic shock at baseline compared to healthy controls. Additionally, HO-1 levels were significantly higher in patients with septic shock compared to patients with severe sepsis. Finally, levels of HO-1 and mtDNA, but not of hemopexin, seemed to slowly revert back towards levels measured in healthy donors within 5 days after admission. Conclusions Our results indicate that plasma levels of the hemoprotein scavengers hemopexin, haptoglobin and HO-1 and the mitochondrial damage marker mtDNA might be useful as additional biomarkers for the early diagnosis of sepsis and disease severity.

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